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Hematology/oncology Clinics of North... Aug 2023With the increasing availability of sequencing techniques and new polymerase chain reaction-based methods, data regarding the genomic profile of Waldenström... (Review)
Review
With the increasing availability of sequencing techniques and new polymerase chain reaction-based methods, data regarding the genomic profile of Waldenström macroglobulinemia (WM) are being continuously analyzed and reproduced. MYD88 and CXCR4 mutations are highly prevalent in all the stages of WM, including the early IgM monoclonal gammopathy of undetermined significance or a more advanced stage, such as smoldering WM. Thus, there is a need to define genotypes before starting either standard treatment regimens or clinical trials. Here, we review the genomic profile of WM and its clinical implications while focusing on recent advances.
Topics: Humans; Waldenstrom Macroglobulinemia; Monoclonal Gammopathy of Undetermined Significance; Lymphoma, B-Cell; Mutation; Myeloid Differentiation Factor 88; Genomics
PubMed: 37211494
DOI: 10.1016/j.hoc.2023.04.002 -
American Journal of Kidney Diseases :... Sep 2023C3 glomerulopathy (C3GN) and atypical hemolytic uremic syndrome (aHUS) are 2 distinct rare kidney diseases caused by dysregulation of the alternative complement pathway....
RATIONALE & OBJECTIVE
C3 glomerulopathy (C3GN) and atypical hemolytic uremic syndrome (aHUS) are 2 distinct rare kidney diseases caused by dysregulation of the alternative complement pathway. Patients with C3GN and concurrent kidney lesions of thrombotic microangiopathy (TMA) have been rarely reported. We characterized the clinical features and underlying immunological abnormalities in these patients.
STUDY DESIGN
Case series.
SETTING & PARTICIPANTS
Patients with C3GN and concomitant TMA lesions on biopsy registered from 2009 to 2019 in the French National Registry of C3GN.
FINDINGS
Among 278 registered patients with C3GN, 16 (6%) had biopsy-proven glomerular and/or vascular TMA lesions. Their median age at diagnosis was 39 years (range, 7-76), and 59% were female. Fourteen of the 16 patients (88%) had an estimated glomerular filtration rate of<30mL/min/1.73m and 3 of 16 (19%) required dialysis. Twelve of the 14 evaluated patients (86%) showed evidence of mechanical hemolysis. Fifty percent of the patients had low C3 levels. Six of the 14 evaluated patients had a rare variant in complement genes, and 4 of the 16 patients (25%) had monoclonal gammopathy. Among the 16 patients, 10 (63%) received eculizumab, 5 (31%) received immunosuppressive therapy, and 4 (25%) received clone-targeted chemotherapy. Median kidney survival was 49 months.
LIMITATIONS
Small retrospective case series with a limited number of biopsies including electron microscopy.
CONCLUSIONS
Concomitant C3GN and TMA is extremely rare and is associated with poor kidney outcomes. Genetic or acquired abnormalities of the alternative complement pathway are common as is the presence of monoclonal gammopathy, which may inform the selection of treatment approaches.
Topics: Humans; Female; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Male; Retrospective Studies; Kidney; Atypical Hemolytic Uremic Syndrome; Thrombotic Microangiopathies; Paraproteinemias
PubMed: 37061020
DOI: 10.1053/j.ajkd.2022.12.020 -
Hematology/oncology Clinics of North... Aug 2023The immunoglobulin M (IgM)-associated peripheral neuropathies (PN) are a heterogeneous group of disorders representing most paraproteinemic neuropathy cases. They are... (Review)
Review
The immunoglobulin M (IgM)-associated peripheral neuropathies (PN) are a heterogeneous group of disorders representing most paraproteinemic neuropathy cases. They are associated with IgM monoclonal gammopathy of undetermined significance (MGUS) or Waldenström macroglobulinemia. Establishing a causal link between a paraprotein and neuropathy can be challenging but is necessary to adopt an appropriate therapeutic approach. The most common type of IgM-PN is Antimyelin-Associated-Glycoprotein neuropathy, but half of the cases are of other causes. Progressive functional impairment is an indication for treatment, even when the underlying disorder is IgM MGUS, involving either rituximab monotherapy or combination chemotherapy to achieve clinical stabilization.
Topics: Humans; Peripheral Nervous System Diseases; Drug Therapy, Combination; Immunoglobulin M; Monoclonal Gammopathy of Undetermined Significance; Rituximab
PubMed: 37385714
DOI: 10.1016/j.hoc.2023.04.007 -
Hematology/oncology Clinics of North... Apr 2024Immunocompetent mouse models of multiple myeloma (MM) are particularly needed in the era of T cell redirected therapy to understand drivers of sensitivity and... (Review)
Review
Immunocompetent mouse models of multiple myeloma (MM) are particularly needed in the era of T cell redirected therapy to understand drivers of sensitivity and resistance, optimize responses, and prevent toxicities. Three mouse models have been extensively characterized: the Balb/c plasmacytomas, the 5TMM, and the Vk*MYC. In the last year, additional models have been generated, which, for the first time, capture primary MM initiating events, like MMSET/NSD2 or cyclin D1 dysregulation. However, the long latency needed for tumor development and the lack of transplantable lines limit their utilization. Future studies should focus on modeling hyperdiploid MM.
Topics: Mice; Animals; Humans; Multiple Myeloma; Disease Models, Animal
PubMed: 38233233
DOI: 10.1016/j.hoc.2023.12.014 -
Hematology/oncology Clinics of North... Apr 2024Multiple myeloma is characterized by a highly heterogeneous disease distribution within the bone marrow-containing skeletal system. In this review, we introduce the... (Review)
Review
Multiple myeloma is characterized by a highly heterogeneous disease distribution within the bone marrow-containing skeletal system. In this review, we introduce the molecular mechanisms underlying clonal heterogeneity and the spatio-temporal evolution of myeloma. We discuss the clinical impact of clonal heterogeneity, which is thought to be one of the biggest obstacles to overcome therapy resistance and to achieve cure.
Topics: Humans; Multiple Myeloma; Bone Marrow; Clonal Evolution
PubMed: 38195308
DOI: 10.1016/j.hoc.2023.12.012 -
Clinical Advances in Hematology &... Sep 2023Multiple myeloma (MM) is a clonal plasma cell dyscrasia and the most common form of primary bone marrow cancer. Nearly 35,000 new cases of MM are diagnosed in the United... (Review)
Review
Multiple myeloma (MM) is a clonal plasma cell dyscrasia and the most common form of primary bone marrow cancer. Nearly 35,000 new cases of MM are diagnosed in the United States each year. MM is a slowly progressive illness that remains incurable. The median survival for patients with MM is approximately 7 years, during which these patients suffer substantial morbidity. Despite the introduction of new drugs and immune-based therapies, many patients unfortunately relapse and require further therapies. Therefore, it is becoming increasingly important to be able to accurately and quickly determine changes in a patient's clinical status. Assessments of monoclonal protein and serum free light chain levels are the most common tests now available for monitoring patients with MM; however, these assays have several drawbacks. Modern radiologic techniques such as positron emission tomography and computed tomography are better than standard radiographs but are costly and cumbersome. Serum B-cell maturation antigen is a new biomarker for both the diagnosis and prognosis of MM. Assessment of measurable residual disease is becoming an important endpoint. The creation of better ways to predict outcomes and promptly and accurately monitor changes for patients with MM should lead to improved quality of life and longer survival.
Topics: Humans; Multiple Myeloma; Quality of Life; Antibodies, Monoclonal; B-Cell Maturation Antigen; Neoplasm, Residual
PubMed: 37647495
DOI: No ID Found -
Blood Cancer Journal Dec 2023Monoclonal gammopathy of undetermined significance (MGUS) is the earliest discernible stage of multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). Early...
Immunophenotypic assessment of clonal plasma cells and B-cells in bone marrow and blood in the diagnostic classification of early stage monoclonal gammopathies: an iSTOPMM study.
Monoclonal gammopathy of undetermined significance (MGUS) is the earliest discernible stage of multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). Early diagnosis of MG may be compromised by the low-level infiltration, undetectable to low-sensitive methodologies. Here, we investigated the prevalence and immunophenotypic profile of clonal (c) plasma cells (PC) and/or cB-lymphocytes in bone marrow (BM) and blood of subjects with a serum M-component from the iSTOPMM program, using high-sensitive next-generation flow cytometry (NGF), and its utility in the diagnostic classification of early-stage MG. We studied 164 paired BM and blood samples from 82 subjects, focusing the analysis on: 55 MGUS, 12 smoldering MM (SMM) and 8 smoldering WM (SWM). cPC were detected in 84% of the BM samples and cB-lymphocytes in 45%, coexisting in 39% of cases. In 29% of patients, the phenotypic features of cPC and/or cB-lymphocytes allowed a more accurate disease classification, including: 19/55 (35%) MGUS, 1/12 (8%) SMM and 2/8 (25%) SWM. Blood samples were informative in 49% of the BM-positive cases. We demonstrated the utility of NGF for a more accurate diagnostic classification of early-stage MG.
Topics: Humans; Plasma Cells; Bone Marrow; Paraproteinemias; B-Lymphocytes; Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance; Waldenstrom Macroglobulinemia; Smoldering Multiple Myeloma
PubMed: 38072838
DOI: 10.1038/s41408-023-00944-1 -
Haematologica May 2024
Topics: Humans; Multiple Myeloma
PubMed: 37981890
DOI: 10.3324/haematol.2023.284292 -
Nature Communications Sep 2023Multiple myeloma (MM) is a hematological malignancy that is consistently preceded by an asymptomatic condition, monoclonal gammopathy of undetermined significance...
Multiple myeloma (MM) is a hematological malignancy that is consistently preceded by an asymptomatic condition, monoclonal gammopathy of undetermined significance (MGUS). Disparities by age, gender, and race/ethnicity in both MGUS and MM are well-established. However, it remains unclear whether these disparities can be explained by increased incidence of MGUS and/or accelerated progression from MGUS to MM. Here, we fit a mathematical model to nationally representative data from the United States and showed that the difference in MM incidence can be explained by an increased incidence of MGUS among male and non-Hispanic Black populations. We did not find evidence showing differences in the rate of progression from MGUS to MM by either gender or race/ethnicity. Our results suggest that screening for MGUS among high-risk groups (e.g., non-Hispanic Black men) may hold promise as a strategy to reduce the burden and MM health disparities.
Topics: Humans; Asymptomatic Diseases; Hematologic Neoplasms; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Health Status Disparities; Sex Factors; Racial Groups; Ethnicity
PubMed: 37730703
DOI: 10.1038/s41467-023-41223-8 -
Hematology/oncology Clinics of North... Aug 2023Waldenström macroglobulinemia (WM) is a rare, indolent, and currently incurable B-cell neoplasm characterized by monoclonal immunoglobulin M gammopathy, frequent nodal... (Review)
Review
Waldenström macroglobulinemia (WM) is a rare, indolent, and currently incurable B-cell neoplasm characterized by monoclonal immunoglobulin M gammopathy, frequent nodal involvement, and lymphoplasmacytic infiltration of the bone marrow. The clinical pattern at diagnosis is similar to that reported in developed countries but, unfortunately, the tools for a complete diagnosis and access to novel therapies are suboptimal. Older drugs such as bendamustine, cyclophosphamide, and chlorambucil may still play a role in treating WM. Prospective studies in resource-limited regions are required to further evaluate these essential aspects of the disease. In this document, we issue recommendations based on our local reality.
Topics: Humans; Waldenstrom Macroglobulinemia; Prospective Studies; Cyclophosphamide; Immunoglobulin M; Bone Marrow
PubMed: 37258356
DOI: 10.1016/j.hoc.2023.04.010